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Endocrinology, doi:10.1210/en.2005-1226
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Endocrinology Vol. 147, No. 4 2043-2050
Copyright © 2006 by The Endocrine Society

Central Effects of Calcitonin Receptor-Stimulating Peptide-1 on Energy Homeostasis in Rats

Hirotake Sawada, Hideki Yamaguchi, Takuya Shimbara, Koji Toshinai, Muhtashan S. Mondal, Yukari Date, Noboru Murakami, Takeshi Katafuchi, Naoto Minamino, Hiroyuki Nunoi and Masamitsu Nakazato

Department of Pediatrics (H.S., H.N.) and Third Department of Internal Medicine (H.Y., T.S., K.T., M.M., Y.D., M.N.), Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692, Japan; Department of Veterinary Physiology (N.M.), Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and Department of Pharmacology, National Cardiovascular Center Research Institute (T.K., N.M.), Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Masamitsu Nakazato, M.D., Ph.D., Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. E-mail: nakazato{at}med.miyazaki-u.ac.jp.

The CT-R [calcitonin (CT) receptor] is expressed in the central nervous system and is involved in the regulation of food intake, thermogenesis, and behaviors. CT-R-stimulating peptide-1 (CRSP-1), a potent ligand for the CT-R, was recently isolated from the porcine brain. In this study, we first confirmed that porcine CRSP-1 (pCRSP-1) enhanced the cAMP production in COS-7 cells expressing recombinant rat CT-R, and then we examined the central effects of pCRSP-1 on feeding and energy homeostasis in rats. Intracerebroventricular (icv) administration of pCRSP-1 to free-feeding rats suppressed food intake in a dose-dependent manner. Chronic icv infusion of pCRSP-1 suppressed body weight gain over the infusion period. Furthermore, icv administration of pCRSP-1 increased body temperature and decreased locomotor activity. The central effects of pCRSP-1 were more potent than those of porcine CT in rats. In contrast, ip administration of pCRSP-1 did not elicit any anorectic or catabolic effects. Administration icv of pCRSP-1 also induced mild dyskinesia of the lower extremities and decreased gastric acid output. Fos expression induced by icv administration of pCRSP-1 was detected in the neurons of the paraventricular nucleus, dorsomedial hypothalamic nucleus, arcuate nucleus, locus coeruleus, and nucleus of solitary tract, areas that are known to regulate feeding and energy homeostasis. Administration icv of pCRSP-1 increased plasma concentrations of ACTH and corticosterone, implying that the hypothalamic-pituitary-adrenocortical axis might be involved in catabolic effects of pCRSP-1. These results suggest that CRSP-1 can function as a ligand for the CT-R and may act as a catabolic signaling molecule in the central nervous system.




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E. Tavares, R. Maldonado, and F. J. Minano
N-Procalcitonin: Central Effects on Feeding and Energy Homeostasis in Rats
Endocrinology, April 1, 2007; 148(4): 1891 - 1901.
[Abstract] [Full Text] [PDF]




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